Preserving personal care products from microbial degradation is quite challenging. Most topical cosmetics and dermatological products in the form of creams, lotions, gels, shampoos, body-washes and face-washes contain significant amount of water in them that provides a very hospitable environment for the microbial growth. In addition to water, the other cosmetic ingredients can also be a good source of nutrients to microbes. Another pertinent point to be reckoned here is that the shelf-life of the personal care products and the period after opening the container by the consumer is quite long compared to pharmaceutical products or food products. Unlike pharmaceuticals, cosmetic products are neither sterilized and nor packed in hermetic conditions. Thus, the requirement for the preservation of the personal care products is indeed quite challenging. This is further compounded by the limited choice of antimicrobials since the available approved antimicrobials are very few and those which have good antimicrobial activity are quite toxic. Consumers want products meant for topical applications to be free from toxic antimicrobials that are used as preservatives. All the current very effective antimicrobials are involved in serious controversies. For example, parabens are implicated in disrupting endocrine system, ultimately linked to breast cancer [(Pharmacology & Toxicology (Vol. 86(3), pp 110-13, March 2000, Toxicology and Applied Pharmacology (Vol. 153(1), pp. 12-19 (November 1998), Journal of Veterinary Medical Science (Vol. 64(3), pp. 227-35 (March 2002, Journal of Applied Toxicology, 24 (3): 167-176, (2004)]. Formaldehyde is classified as Category 3 CMR (carcinogenic, mutagenic and reproductive toxicity) and hence all formaldehyde releasers are under the cloud. This class includes the work-horse preservatives like DMDM hydantoin, diazolidinyl urea, imidazolidinyl urea and Quaternary 15.
Another class of very effective antimicrobials is ‘isothiazolinones’. Methyl and Chloromethyl isothiazolinones have been used in personal care but they have been reported to be neurotoxic and skin sensitizers (Journal of Neuroscience 22 (17): 7408-7416. The Lancet, Volume 333, Issue 8633, Pages 314-316 (1989).
Halogenated molecules have their own share of controversies. For example, there is a big movement against trichlosan. It is a phenolic and halogenated molecule and has been implicated in ecotoxicity (algae, dolphins). It is reported to be an endocrine disrupter (thyroid function) and is reported to impair cardiac and skeletal muscles. There seems to a special concern for children who are at higher risk of allergies and the immune systems (Toxicological Sciences, 2009, 107 (1): 56-64, Reproductive Toxicology, April 2009, 27(2):177-185). Company like Johnson and Johnson has removed it from its products and P & G will be doing the same by the end of 2014. Reckitt Benckiser is phasing it out from its products too. Iodopropynyl butyl carbamate, another halogenated antimicrobial, is a contact allergen (American Journal of contact dermatitis 13(2), 77-79 (2002). Presence of iodine in the molecular structure gets it implicated in Goiter and malfunctioning thyroid gland. It has not been allowed in Japan and in European Union (EU) it is allowed only up to 0.02% in leave-on products. Similarly, EU permits usage of methyl dibromo glutaronitrile only up to 0.1% and that too in only rinse-off products. Halogenated molecule like Bronopol, very widely used once upon a time, however, is banned today in countries like Canada for its usage in cosmetics. It is involved in allergic reactions as well as generation of N-nitroso amine that are known to be carcinogenic. The quaternary ammonium compounds (examples are cetyl pyridinium chloride, benzethonium chloride, benzalkonium chloride) exhibit good antimicrobial activity but their utility in personal care industry is limited due to specific incompatibilities with other cosmetic ingredients, particularly with the ingredients of strong anionic nature.
In summary, the major work-horse preservatives of personal care industry are being phased out and industry is looking for a solution, a preservation system that is efficacious, safe and globally accepted. The antimicrobials available to personal care industry other than these five major classes of work-horses (parabens, isothiazolinones, formaldehyde releasers, halogenated molecules and quaternary ammonium compounds) are too weak and have a number of limitations. Hence it is important to find a good antimicrobial synergy between non-controversial antimicrobials and other accepted personal care ingredients to offer a broad spectrum of activity against bacteria and fungi meeting the purpose of preservation of finished personal care formulations.
Both, personal care industry and the manufacturers of preservatives are looking for better and safer alternatives for preservation of personal care products. Though discovering a new powerful and toxicologically safe broad spectrum antimicrobial is theoretically possible, it is a long and expensive process to discover a new material and have it approved by the Cosmetics Directives and accepted by the global markets. According to the industry experts, finding an ‘ideal preservative’ is like looking for the biblical “Holy Grail” and the industry has stopped looking for the ‘ideal’ preservative (Donald Orth in ‘Insights into cosmetic microbiology’, Allured Publications, 2010).
Thus, faced with a consumer rebellion against certain categories of preservatives, much of the current effort by the industry has been directed in discovering synergy between mixtures of existing preservatives and in finding personal care ingredients that may have a coincidental antimicrobial activity (John Woodruff, Soap Perfumery and Cosmetics, September, 2006).
Recently, synergistic combinations for enhanced anti-microbial activity of three types of chemical substances, namely, octanoyl component, undecylenoyl component and ‘liquid ether alcohol’, have been reported (Koshti et al., WO 2013076697). Based on the teachings of this patent application it is apparent that combination of phenoxy ethanol, octanoyl glycine and undecylenoyl glycine would form a potential synergistic preservative system. Individually, all the three components are well-established personal care ingredients. Also, there have been instances where lipidated glycines, N-capryloyl glycine, and N-undecylenoyl glycine have been employed together for their derma-protector/derma-purifier effect. In some cases their usage has been suggested to create seemingly ‘preservative-free’ formulations.
U.S. Pat. No. 7,214,391 reports use of around 2.5% N-capryloyl glycine or N-undecylenoyl glycine along with glyceryl laurate and glycol to create seemingly ‘preservative-free’ formulations from botanical extracts such as grape, Irish moss, yucca and green tea etc.
Thus, it can be seen that lipidated glycines are being used either alone or together for topical applications. It has also been suggested that these skin actives can perform the function of preservation. N-Undecylenoyl glycine is reported to possess anti-acne activity, when used along with other ingredients like zinc gluconate, capryloyl glycine, plant extracts from rathania, tea, cinnamon, willows or hamemelis (EP0983055).
As mentioned above, recently, synergy between well-known antimicrobials like phenoxy ethanol, N-capryloyl glycine and undecylenoyl monoethanolamide for preservation of personal care products has been reported (WO 2013076697).
However, though expected, the synergy between lipidated glycines and phenoxy ethanol has not been reported so far, particularly, N-undecylenoyl glycine, N-capryloyl glycine and phenoxy ethanol for anti-microbial preservation of personal care ingredients.
Therefore, the present invention aims to provide stable, synergistic, efficacious preservative compositions made up of well accepted personal care ingredients. The proposed compositions are free of controversial parabens, formaldehyde donors, phenolic compounds, halogenated molecules and quaternary ammonium molecules.